DESCRIPTION (provided by investigator): COPD and pneumonia are among the leading causes of morbidity and mortality in adults 60 years and older, and pneumonia rates are higher for those with COPD. Asthma often coexists with COPD in adults and worsens COPD progression. The current modalities for treatment of COPD are limited, and prevalence of vitamin D deficiency is high. COPD lung disease (COPD, asthma, airflow obstruction), and most COPD additional co-morbidities responsible for COPD progression (e.g., respiratory infections/pneumonia, muscle weakness, cardiac failure) may benefit from vitamin D supplementation therapy but this requires rigorous testing. Marine omega-3 fatty acids work through different pathways from vitamin D to modulate inflammation. We have carefully evaluated the dose of each of these supplements to achieve the best balance of efficacy and safety. Observational studies and clinical trials suggest that fish consumption and EPA or DHA may protect against COPD, asthma or pneumonia, but data are not consistent. Thus there is a compelling rationale for a clinical trial to evaluate the potential benefits or risks of vitamin D and marine omega-3 fatty acid supplementation on COPD and asthma exacerbations, airflow obstruction and decline of lung function, and risk of pneumonia. We propose to take advantage of a large-scale randomized clinical trial-the VITamin D and OmegA-3 TriaL (VITAL), whose endpoints are primary prevention of cancer and cardiovascular diseases-to conduct the first major evaluation of the role of vitamin D and long-chain marine omega-3 polyunsaturated fatty acid (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) supplementation on obstructive and infectious respiratory disease outcomes. VITAL is a cost-effective, randomized, double-blind, placebo- controlled clinical trial among 20,000 men and women without cancer or CVD at baseline, who are selected on age only (men aged e60 and women aged e65), with an oversampling of blacks. In a 2x2 factorial design, participants will be randomized to moderate-to-high dose vitamin D3 (cholecalciferol; 1600 IU [40 5g]/d) and fish oil (EPA [500 mg/d] + DHA [500 mg/d]) supplements (or placebos) independently. We hypothesize that Vitamin D3 and marine omega-3 fatty acid (EPA+DHA) supplementation will result in reduction of COPD and asthma exacerbations; in reduction in decline of lung function; in improvement of airway obstruction and asthma control; and in reduction of pneumonia in adults. To test our Lung VITAL hypotheses it is essential to complete pre-randomization assessment of baseline respiratory symptom status, COPD and asthma exacerbations in the past year; asthma control and use of controller and rescue medication; pulmonary function; and baseline vitamin D and fatty acid levels. Thus it is critically important that this ancillary study be undertaken in parallel to the enrollment period for the parent VITAL trial (Appendix B), which is scheduled to begin in January 2010.